Studies in the Lens and Cataract Biology Section are focussed on the biology of the normal lens and on elucidating mechanisms underlying the process of aging-related cataractogenesis. During the past year work has concentrated on aspects of signal transduction involving the Ras superfamily of small GTPases, proteins which act as molecular switches regulating many critical cellular functions. Dr. Qiu- fang Cheng has been working toward isolating and characterizing a novel group of GTP binding proteins which appear to be unique to lens fiber cells. We believe that these particular proteins may be involved in the process through which lens fibers differentiate from lens epithelial cells and ultimately become denucleated, mature fibers. In addition, we have been investigating the significance to lens functional integrity of isoprenylation, a post-synthetic modification essential for the proper function of most small GTPases. We have shown that blocking isoprenylation with different inhibitors causes cataract in model systems. Dr. Rachel Neal, who recently joined the Section, has initiated efforts to isolate an enzyme previously detected in the lens which utilizes the reducing equivalents of pyridine nucleotides to inactivate reactive oxygen species. This enzyme may be a primary part of the lens defense mechanisms against oxidative damage. - lens, cataract, aging, small GTPases,oxidative stress, isoprenoids